Mutator tRNAs are Encoded by the Escherichia coli Mutator Genes mutA and mutC: A Novel Pathway for Mutagenesis

We have previously described the mutator alleles mutA and mutC, which map at 95 minutes and 42 minutes, respectively, on the Escherichia coli genetic map and which stimulate transversions; the A· T → T· A and G· C → T· A substitutions are the most prominent. In this study we show that both mutA and...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (9), p.4380-4385
Main Authors: Slupska, Malgorzata M., Baikalov, Claudia, Lloyd, Robert, Miller, Jeffrey H.
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Sequence
Anticodon
Aspartic Acid
Bacteria
Base Composition
Base Sequence
Cloning, Molecular
Codons
Complementation
DNA
DNA Primers
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Genes, Bacterial
Genetic Complementation Test
Genetic loci
Genetic mutation
Genetics
Glycine
Molecular Sequence Data
Mutagenesis
Mutation
Phenotypes
Plasmids
Polymerase Chain Reaction
Restriction Mapping
Ribonucleic acid
RNA
RNA, Transfer - biosynthesis
RNA, Transfer, Gly - biosynthesis
RNA, Transfer, Gly - genetics
Transfer RNA
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Summary:We have previously described the mutator alleles mutA and mutC, which map at 95 minutes and 42 minutes, respectively, on the Escherichia coli genetic map and which stimulate transversions; the A· T → T· A and G· C → T· A substitutions are the most prominent. In this study we show that both mutA and mutC result from changes in the anticodon in one of four copies of the same glycine tRNA, at either the glyV or the glyW locus. This change results in a tRNA that inserts glycine at aspartic acid codons. In view of previous studies of missense suppressor tRNAs, the mistranslation of aspartic acid codons is assumed to occur at ≈ 1-2%. We postulate that the mutator tRNA effect is exerted by generating a mutator polymerase and suggest that the ε subunit of DNA polymerase, which provides a proofreading function, is the most likely target. The implications of these findings for the contribution of mistranslation to observed spontaneous mutation rates in wild-type strains, as well as other cellular phenomena such as aging, are discussed.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.9.4380